Ronald C. Arndorfer

Mechanism of gastroesophageal reflux in recumbent asymptomatic human subjects.

We investigated the mechanism of gastroesophageal reflux (GER) in 10 health volunteer subjects. Continuous recordings of intraluminal esophageal pH and pressure were obtained on two consecutive nights from 6:00 p.m. to 6:30 a.m. in each subject. During each study, the subject remained recumbent, except to eat a standardized meal after 1 h of basal recording. A manometric assembly with seven recording lumens monitored: (a) lower esophageal sphincter (LES) pressure via a sleeve device 6.5 cm in length, (b) esophageal-body motor activity, (c) swallowing activity in the pharynx, and (d) gastric pressure. An electrode 5 cm above the LES recorded esophageal pH. Sleep was monitored by electroencephalogram. All subjects showed wide variations of basal LES pressure. GER was not related to low steady-state basal LES pressure, but rather occurred during transient 5-30 s episodes of inappropriate complete LES relaxation. The inappropriate LES relaxations were usually either spontaneous or immediately followed appropriate sphincter relaxation induced by swallowing. The majority of GER episodes occurred within the first 3 h after eating. During the night LES relaxation and GER occurred only during transient arousals from sleep or when the subjects were fully awake, but not during stable sleep. After GER the esophagus was generally cleared of refluxed acid by primary peristalsis and less frequently by secondary peristalsis. Nonperistaltic contractions were less effective than peristalsis for clearing acid from the esophagus. We conclude that in asymptomatic recumbent subjects GER is related to transient inappropriate LES relaxations rather than to low steady-state basal LES pressure and also, that primary perstalsis is the major mechanism that clears the esophagus of refluxed material.

Esophageal Peristaltic Dysfunction in Peptic Esophagitis

Esophageal exposure to acid is a major determinant in the pathogenesis of reflux esophagitis. In this study, we analyzed the esophageal peristaltic function of 177 patients and asymptomatic volunteers for abnormalities that could lead to prolonged esophageal acid clearance. The subjects were divided into five groups: normal volunteers, patient controls, patients with noninflammatory gastroesophageal reflux disease, patients with mild esophagitis, and ones with severe esophagitis. Manometric data were analyzed for the occurrence of failed primary peristalsis, for the occurrence of feeble peristalsis in the distal esophagus, and for hypotensive lower esophageal sphincter pressure. From an analysis of the data on control patients, peristaltic dysfunction was defined as the occurrence of either failed primary peristalsis or hypotensive peristalsis in the distal esophagus for over half of the test swallows. Peristaltic dysfunction was increasingly prevalent with increasing severity of peptic esophagitis, occurring in 25% of patients with mild esophagitis and 48% of patients with severe esophagitis. A correlation did not exist between the occurrence of peristaltic dysfunction and hypotensive lower esophageal sphincter pressure (less than or equal to 10 mmHg). We conclude that peristaltic dysfunction occurs in a substantial minority of patients with peptic esophagitis and could contribute to increased esophageal exposure to refluxed acid material.

Effect of sleep, spontaneous gastroesophageal reflux, and a meal on upper esophageal sphincter pressure in normal human volunteers

Owing to the inherent difficulties of recording upper esophageal sphincter pressure, little is known about normal upper esophageal sphincter physiology. In this study we used a modified sleeve device to record upper esophageal sphincter pressure continuously in 8 normal volunteers. Intraesophageal pH and electroencephalogram activity were also recorded to document the occurrence of spontaneous gastroesophageal reflux and sleep. After an hour of baseline recording, the subjects ate a meal. Recording was then resumed for an additional 7 h during which period the subjects slept part of the time. The mean upper esophageal sphincter pressure was measured for each 10-min epoch. Electroencephalogram recordings were read blindly for the presence and stage of sleep. Periods of sleep were then correlated with the manometric tracings. Mean upper esophageal sphincter pressure during wakefulness, stage 1 sleep, and deeper sleep was 40 +/- 17 (SD), 20 +/- 17, and 8 +/- 3 mmHg, respectively. A significant change in upper esophageal sphincter pressure did not occur postprandially or during episodes of spontaneous gastroesophageal reflux. Upper esophageal sphincter pressure was observed to increase transiently with each inspiration during periods of restfulness and sleep, a response consistent with the hypothesis that one function of the upper esophageal sphincter is to exclude air from the esophagus during respiration. The demonstration that upper esophageal sphincter pressure falls markedly during sleep may have significance in that this diminishes the barrier to nocturnal regurgitation and potential aspiration.

Coordination of deglutitive glottic closure with oropharyngeal swallowing

The goals of this study were to quantify the temporal relationship between swallow-induced glottic closure and (a) signals of swallow initiation, such as hyoid bone movement, tongue base movement, and mylohyoid electrical activity; (b) pharyngeal peristalsis; (c) laryngeal elevation; (d) vestibular closure; and (e) oropharyngeal barium bolus transit. Eight normal subjects (age 20-30 yr) were studied by concurrent transnasal video laryngoscopy, pharyngeal intraluminal manometry, and submental surface electromyography. The manometric, electromyographic, and both video recordings were synchronized with one another using a specially designed event marker. Dry, 5-ml water, and 5-ml barium swallows were recorded. Frame-by-frame analysis of the video endoscopic recordings showed that deglutitive laryngeal kinetics consisted of vocal cord adduction associated with transverse approximation of the arytenoids followed by vertical approximation of arytenoids to the base of the epiglottis followed by laryngeal ascent and epiglottic descent. Onset of swallow-induced vocal cord adduction preceded the onset of hyoid bone movement, base of the tongue movement, and submental surface myoelectric activity by 0.33 +/- 0.04 (SE) s, 0.31 +/- 0.04 s, and 0.38 +/- 0.04 s, respectively. Onset of vocal cord adduction also preceded the initiation of peristalsis in the nasopharynx and its propagation to oropharynx and upper esophageal sphincter by 0.64 +/- 0.05 s, 0.82 +/- 0.05 s, and 1.08 +/- 0.04 s, respectively. The time between the onset of vocal cord adduction and their return to full opening was 2.2 +/- 0.09 s. It was concluded that (a) among events evaluated, vocal cord adduction is the initial event during the swallowing sequence; (b) laryngeal kinetics during deglutition have distinctive features, and their close coordination with other swallowing events suggests that they are an essential feature of the swallowing program; and (c) abnormal laryngeal kinetics or lack of coordination between the glottic closure mechanism and oropharyngeal bolus transport may have an important role in swallow-induced aspiration.

Integrity of cholinergic innervation to the lower esophageal sphincter in achalasia

The human lower esophageal sphincter (LES) is believed to be innervated by nonadrenergic, noncholinergic inhibitory nerves, and cholinergic excitatory nerves. In idiopathic achalasia, LES relaxation is abnormal because the inhibitory nerves to the sphincter are either absent or functionally impaired. The integrity of cholinergic excitatory nerves to the LES, however, has not been thoroughly evaluated. In 27 patients with untreated idiopathic achalasia, and 21 healthy volunteers, we investigated the hypothesis that postganglionic cholinergic nerves to the LES are functionally intact in achalasia. The LES responses to atropine, edrophonium, methacholine, amyl nitrite, and pentagastrin were assessed. In 2 achalasia patients, patterns of fasting motor activity in the LES were investigated during overnight manometric studies. Resting LES pressure was significantly greater in the achalasia patients, 41 +/- 4 mmHg (mean +/- SE), than in the normal subjects, 20 +/- 2 mmHg. Atropine significantly reduced LES pressure in both groups by 30%-75%. Edrophonium increased LES pressure in the achalasia patients but had negligible effect on the normal subjects. The LES in achalasia patients exhibited an increased sensitivity to both methacholine and pentagastrin compared with the normal subjects. In both patients who underwent an overnight manometric study, the LES exhibited cyclic phasic contractile activity synchronous with gastric contractions during the migrating motor complex. We conclude that the study findings support the hypothesis that postganglionic cholinergic LES innervation in achalasia patients is either normal or only minimally impaired, in contrast to the marked impairment of the inhibitory nerves governing LES relaxation.

Upper esophageal sphincter function during belching

We studied the mechanism of belching with specific attention to the upper esophageal sphincter (UES) in 14 normal volunteers. Belching occurred by the following sequence of events: lower esophageal sphincter relaxation; gastroesophageal gas reflux, recorded manometrically as a gastroesophageal common cavity phenomenon; UES relaxation; esophagopharyngeal gas reflux; and restoration of intraesophageal pressure to baseline by a peristaltic contraction. Upper esophageal sphincter relaxations comparable to those associated with belches were induced by abrupt esophageal distention with air boluses. In contrast, fluid boluses injected into the midesophageal body either had no effect on UES pressure or increased UES pressure. Thus, the UES responded to esophageal body distention in two distinct ways: abrupt relaxation in response to air boluses and pressure augmentation in response to fluid boluses. Mucosal anesthesia did not alter the UES response to esophageal boluses of gas or liquid thereby making it unlikely that these substances are differentiated by a mucosal receptor. Rapid distention of the proximal esophagus with a cylindrical balloon (15 cm long) elicited UES relaxation. These findings suggest that the rapidity and spatial pattern of esophageal distention, rather than discrimination of the type of material causing the distention, determines whether or not UES relaxation occurs.

Mechanisms of gastroesophageal reflux in children

We studied the lower esophageal sphincter in 29 children with known or suspected gastroesophageal reflux using a sleeve sensor and micro pH electrode. Mean lower esophageal sphincter pressure for a ten-minute monitoring period was 19 +/- 13 mm Hg; however, considerable temporal variation occurred in each child. Gastroesophageal reflex was infrequently associated with a low basal sphincter pressure (< 5 mm Hg) but usually associated with an increase in intra-abdominal pressure or with transient inappropriate relaxation of the lower esophageal sphincter.

Pharyngeal acid reflux events in patients with vocal cord nodules

Objective: Gastroesophageal reflux has been implicated in the pathogenesis of vocal cord nodules. However, a cause‐and‐effect relationship has not been established. Because documentation of pharyngeal acid reflux events makes this correlation more plausible, the aim of the present study was to determine the frequency of pharyngeal acid reflux events in patients with vocal cord nodules. Methods: Eleven patients with vocal cord nodules (mean age, 42 ± 6 years) and eleven healthy volunteers (mean age, 45 ± 6 years) were studied. Patients underwent barium esophagram and ambulatory 24‐hour simultaneous three‐site pharyngo‐esophageal pH monitoring. Controls only had ambulatory 24‐hour simultaneous three‐site pH monitoring. In the ambulatory pH monitoring studies, pH was recorded from the manometrically determined sites of pharynx (2 cm above upper esophageal sphincter), proximal esophagus (10 cm distal to pharyngeal site), and distal esophagus (5 cm above the lower esophageal sphincter). Pharyngeal acid reflux event was deemed acceptable if all three sites recorded a decrease in pH below 4 which was not related to meal or drinking. Results: Pharyngeal acid reflux events occurred in seven of 11 patients with vocal cord nodules (1–4 episodes) and two of 11 controls (1–2 episodes) (P < .05). In both groups all pharyngeal acid reflux events occurred in upright position and were not associated with belching or coughing. Barium studies documented hiatal hernia in two patients and gastroesophageal reflux in five of 11 patients. However, none of the esophageal reflux events reached the pharynx on barium esophagram. Conclusions: Prevalence of pharyngeal acid reflux events is significantly higher in patients with vocal cord nodules compared with normal controls and suggests a contributory role for gastroesophagopharyngeal acid reflux in the pathogenesis of some vocal cord nodules.

Esophagoglottal closure reflex: A mechanism of airway protection

Abrupt esophageal distention occurs commonly during gastroesophageal reflux, thereby generating a circumstance favorable to esophagopharyngeal regurgitation and laryngeal aspiration of gastric refluxate. The aims of the present study were to examine the glottal response to esophageal distention by air and regional esophageal distention by a balloon. Fifteen healthy volunteers (age, 25 +/- 5 years) were studied while they were in an upright position. Using concurrent videoendoscopy and manometry, glottal and upper esophageal sphincter (UES) responses to abrupt esophageal distention by air injection (10-60 mL) and balloon distention (1.5, 2.0, and 2.5 cm) were recorded simultaneously. In addition, 6 subjects were studied with concurrent synchronized videofluoroscopy. Results showed that esophageal distention by air at a threshold volume of 10-60 mL caused vocal cord closure. The UES response to this threshold volume was variable. Volumes larger than the threshold value caused complete UES relaxation and belching. In addition to vocal cord closure, belching was accompanied by anterior movement of the glottis. On videofluoroscopy, the hyoid bone moved anteriorly in association with belching, but not with vocal cord closure without belching. Proximal esophageal distention by the balloon also provoked vocal cord closure. This response was less consistent for balloon distention in the middle and distal esophagus. It is concluded that (a) esophageal distention by either air or a balloon evokes a glottal closure mechanism, thereby suggesting the existence of an esophagoglottal reflex; (b) this reflex is elicited most easily by distention of the proximal esophagus; (c) glottal and UES responses to esophageal distention are independent from each other; and (d) the esophagoglottal closure reflex may play an important role in preventing laryngeal aspiration of acid due to gastroesophageal reflux accompanied by acid regurgitation into the pharynx.

A method for continuous monitoring of upper esophageal sphincter pressure

We tested a manometric assembly employing a sleeve sensor that is able to monitor anterior or posterior pressure in the human upper esophageal sphincter (UES) for prolonged intervals. When compared to rapid pull-through measurement of UES pressure obtained with conventional manometric assemblies, the sleeve sensor measured significantly lower UES pressures with less variability between subjects, thereby suggesting that the rapid pull-through maneuver stimulates the UES to contract. Concurrent recordings of UES pressure with a sleeve sensor and a side-hole sensor during a slow station pull-through yielded almost equal pressure values at the peak of the high-pressure zone (station zero), but the side-hole site recorded significantly lower pressures than the sleeve at stations 0.5 cm or more from the peak of the high-pressure zone. During 10 min of recording at station zero, the sleeve sensor recorded greater pressures than the side-hole sensor. This finding demonstrated the suceptibility of the side-hole sensor to axial movement relative to peak UES pressure. When stationary, both the sleeve sensor and the side-hole sensor recorded significantly lower UES pressure after 1–2 min of recording, again suggesting that movement of the recording assembly stimulates the UES to contract. Sleeve recordings of swallow-induced UES relaxations showed that UES relaxations induced by water swallows were slightly longer than those induced by dry swallows. Augmentations of UES pressure induced by balloon distension of the esophageal body were also recorded. We conclude that the sleeve sensor is a suitable method for investigating the normal physiology and pathophysiology of the UES in human subjects.